Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are tumors characterized by intraductal proliferation of neoplastic mucinous cells with various degrees of cytologic atypia, which usually form papillae and lead to cystic dilatation of pancreatic ducts, forming clinically detectable masses. Since the first description of IPMN, over the past 30 years, these lesions have been recognized with increasing frequency, accounting for up to 20% of all resected pancreatic specimens in large referral centers. Similarly, a recent study of 2,832 consecutive abdominal CT scans undertaken for indications unrelated to pancreatic disease has found a prevalence of asymptomatic pancreatic cysts to be 2.6% among all comers and 8.7% among those above the age of 80.
Macroscopically, IPMN is classified into main-duct, combined, and branch-duct types based on the differential involvement of the pancreatic duct system. It has been shown that main-duct and combined type IPMNs are more likely to have invasive carcinoma compared to branch-duct type (48% and 42% vs. 11%), and subsequently, 5-year disease specific survival rates of main-duct and combined type IPMNs are significantly lower than that of branch-duct type (65% and 77% vs. 91%). Histologically, IPMN are thought to progress from low-grade dysplasia (adenoma) to intermediate- and high-grade dysplasia (carcinoma in situ) and invasive carcinoma. While the 5-year survival of patients with resected non-invasive IPMN is as high as 77-94%, invasive IPMN carries a much poorer survival of 33-43%. Given the significant difference in survival between invasive and non-invasive IPMNs as well as between main-duct and branch-duct IPMNs, clinical guidelines have been adopted to assist clinicians in determining when a lesion should be surgically resected. However, while sensitive (97-100%), these guidelines have proven to be highly non-specific (23-30%), especially among branch-duct IPMN. Given the prevalence of asymptomatic cysts in an elderly population who tend to have comorbidity, more specific tools that can segregate high-risk and malignant from low-risk lesions are warranted. In an effort to improve diagnostic accuracy, analyses of cyst fluid for genetic changes have been used and several biomarkers including Plectin-1 have been investigated. However, more specific markers of clinically high-risk lesions are needed to aid in the pre-operative diagnosis and risk stratification of patients with IPMN.
Recently, morphologic variations of IPMN have been recognized and criteria established for distinguishing IPMN into four distinct epithelial subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. Similarly, invasive carcinoma arising in IPMN (invasive IPMN) has also been morphologically classified into colloid, tubular, and oncocytic carcinomas. Of those, the gastric-type (IPMN-G) comprises the majority of branch-duct IPMN, and rarely exhibits high-grade dysplasia (carcinoma in situ). Invasion is uncommon, but when it occurs, is usually of tubular type. The intestinal type (IPMN-I) that makes up the majority of the main-duct IPMN often exhibits intermediate- to high-grade dysplasia and is prone to developing invasive carcinoma. Given its propensity to involve the main duct and to develop invasive carcinoma, IPMN-I, even of intermediate grade, may warrant surgical intervention. Both pancreatobiliary and oncocytic (IPMN-O) types are rare, but typically demonstrate high-grade dysplasia and often contain invasive or minimally invasive carcinoma. Despite these efforts, there still is a need for more specific markers.